BioElectroMed is developing a new medical device called the EndoPulse that will deliver nanosecond pulsed electric fields (nsPEF) to treat pancreatic carcinomas. We have extensive evidence supporting the efficacy of nsPEF in eliminating all three types of skin cancer, basal and squamous cell carcinoma and melanoma. The mechanism by which nsPEF causes tumor regression involves increasing the permeability of intracellular membranes and triggering apoptosis. This electric field-induced membrane permeability increase is not cell specific so the same pulse parameters that are effective at eliminating skin tumors should also be effective at treating pancreatic tumors. The main advantage of this nsPEF application over other tumor treatments is that it minimizes damage to healthy tissue surrounding the tumor. Only cells located within the electrode array are stimulated by nsPEF application to undergo apoptosis. The main challenge is the accurate placement of the electrodes around the tumor and this will be accomplished using endoscopic ultrasound (EUS). The EndoPulse electrodes will be inserted down the accessory channel of the endoscope and guided to the tumor using ultrasound imaging. During Phase I of this project we have three specific aims: 1) Fabricate a nanosecond pulsed electric field (nsPEF) electrode compatible with endoscopic ultrasound and capable of applying nsPEF to pancreatic tumors;2) Determine the optimal pulse parameters to use with the EndoPulse electrode to trigger apoptosis in pancreatic tumors using a murine subcutaneous xenograft model;3) Demonstrate safety and feasibility of EUS-guided nsPEF ablation of normal pancreatic tissue in a pig. Phase II will then launch clinical trials at Stanford Medical Center under the direction of Dr. Ann Chen. If the EndoPulse can reliably eliminate pancreatic carcinomas, it would offer a much needed breakthrough in the treatment of this deadly disease. PUBLIC HEALTH RELEVANCE: We are developing a new medical device, the EndoPulse, for treating pancreatic carcinoma for which there are currently no effective therapies. The EndoPulse exposes the tumor to ultrashort electrical pulses which permeabilize intracellular membranes and trigger apoptosis or programmed cell death. This causes pancreatic carcinomas to self-destruct. The EndoPulse is guided to the carcinoma via an accessory channel in an ultrasound imaging endoscope which will also be used to image the placement of the electrodes around the tumor. Endoscopically delivered electrical pulses to trigger tumor remission offers a much needed breakthrough in the treatment of pancreatic cancer.